Blood pressure changes associated with sibutramine and weight management – an analysis from the 6‐week lead‐in period of the sibutramine cardiovascular outcomes trial (SCOUT)*

Sharma, Arya M.; Caterson, Ian D.; Coutinho, Walmir; Finer, Nick; Gaal, Luc Van; Maggioni, Aldo P.; Torp‐Pedersen, Christian; Bacher, Hans Peter; Shepherd, Gillian; James, W. P. T.; Investigators, Scout

doi:10.1111/j.1463-1326.2008.00930.x

Cited by 25 publications

(19 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vital sign changes were assessed post hoc by initial BP categorized as normal, high-normal or hypertensive, weight change categories and current antihypertensive medication class use. [103] In hypertensive patients, BP decreases were observed during 6-week treatment with sibutramine even when body weight was unchanged. In patients with normal BP, weight loss of >5% induced decreases in systolic BP; otherwise, small increases were observed.…”

Section: Sibutramine Cardiovascular and Diabetes Outcome Study (Scout)mentioning

confidence: 99%

See 1 more Smart Citation

Cardiovascular Risk-Benefit Profile of Sibutramine

Scheen

2010

American Journal Cardiovascular Drugs

View full text Add to dashboard Cite

SUMMARYSibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to what was previously reported with some other anti-obesity agents. However, it exerts

show abstract

Section: Sibutramine Cardiovascular and Diabetes Outcome Study (Scout)mentioning

confidence: 99%

“…[102][103][104][105][106][107][108] A total of 10,742 subjects received treatment in the lead-in period; 97% had CVD, 88% hypertension and 84% T2DM. [102] Body weight decreased (median 2.…”

Section: Sibutramine Cardiovascular and Diabetes Outcome Study (Scout)mentioning

confidence: 99%

Cardiovascular Risk-Benefit Profile of Sibutramine

Scheen

2010

American Journal Cardiovascular Drugs

View full text Add to dashboard Cite

show abstract

“…Non-surgical treatments for obesity have included the medications orlistat, sibutramine and rimonabant. Sibutramine has recently been withdrawn from the European market, as a recent study has suggested an increased incidence of cardiovascular events [10]. Similarly, rimonabant was withdrawn due to an associated increase in anxiety and depression [11].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, adverse effects and tolerability of a novel analogue of human pancreatic polypeptide, PP 1420

Tan

Field

Minnion

et al. 2012

Brit J Clinical Pharma

View full text Add to dashboard Cite

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Human pancreatic polypeptide (hPP) is a natural pancreatic hormone that suppresses appetite after meals.• When exogenous hPP is given to healthy human volunteers, it causes a reduction in food intake.• PP 1420 is a longer acting analogue of hPP that has been developed as a novel treatment for obesity.WHAT THIS STUDY ADDS• PP 1420 has been shown to be well tolerated in healthy human volunteers.• PP 1420 has been shown to have an extended terminal elimination half‐life compared with hPP.AIMS The objectives of this phase 1 study were to confirm the tolerability of single ascending subcutaneous doses of PP 1420 in healthy subjects, to assess its adverse effects and to investigate the drug's pharmacokinetics and dose proportionality.METHODS This was a double‐blind, placebo‐controlled, randomized study. There were three dosing periods. Each subject (n= 12) was randomized to receive one dose of placebo and two ascending doses of PP 1420, given as a subcutaneous injection. Blood samples were taken over 24 h to assess pharmacokinetics. Standard safety and laboratory data were collected. The primary endpoint was the tolerability of PP 1420. The secondary endpoint was exposure to PP 1420 as assessed by Cmax and AUC(0,∞).RESULTS PP 1420 was well tolerated by all subjects with no serious adverse effects. Following single subcutaneous doses of PP 1420 at 2, 4 and 8 mg to male subjects, Cmax was reached at a median tmax of approximately 1 h post dose (range 0.32–2.00 h). Thereafter, plasma concentrations of PP 1420 declined with geometric mean apparent terminal elimination t1/2 ranging from 2.42–2.61 h (range 1.64–3.95 h) across all dose levels.CONCLUSIONS Subcutaneous PP 1420 was well tolerated in healthy human subjects at single doses between 2–8 mg, with no tolerability issues arising. Where observed, adverse events were not serious, and there was no evidence of a dose‐relationship to frequency of adverse events. The results therefore support the conduct of clinical trials to investigate efficacy, tolerability and pharmacokinetics during repeated dosing.

show abstract

“…[135]. Heart rates were uniformly elevated (median 1-4 bpm, p \ 0.001) across blood pressure and weight change categories [135]. Effects on heart rate variability were not described, but an independent study [136] in obese obstructive sleep apnea patients reported no impact.…”

Section: Sibutramine a Comparable Drug?mentioning

confidence: 96%

“…In hypertensive patients, blood pressure (mmHg) decreased by a median of 6. [135]. Heart rates were uniformly elevated (median 1-4 bpm, p \ 0.001) across blood pressure and weight change categories [135].…”

Section: Sibutramine a Comparable Drug?mentioning

confidence: 98%

Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?

Antel

Albayrak

Heusch³

et al. 2014

Eur Arch Psychiatry Clin Neurosci

View full text Add to dashboard Cite

With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1 years of follow-up in children and adolescents and mean duration of 0.33 years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH.

show abstract

Blood pressure changes associated with sibutramine and weight management – an analysis from the 6‐week lead‐in period of the sibutramine cardiovascular outcomes trial (SCOUT)*

Cited by 25 publications

References 20 publications

Cardiovascular Risk-Benefit Profile of Sibutramine

Cardiovascular Risk-Benefit Profile of Sibutramine

Pharmacokinetics, adverse effects and tolerability of a novel analogue of human pancreatic polypeptide, PP 1420

Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?

Contact Info

Product

Resources

About